Control of body fat in human and non-human animals is an ongoing concern and many approaches are sought for achieving body fat control. One goal in the meat industry is to increase the percentage of lean meat in animals. It is therefor desirable to reduce animal body fat because, in general a lower body fat level leads to a higher muscle-to-fat ratio. It is also desirable in many situations in the medical and veterinary arts to reduce fat accumulation in adipocytes. For example, in obese human and non-human animals, adipocytes that accumulate excess lipids can become insulin resistant, a characteristic having many adverse effects including the development of diabetes.
Conjugated linoleic acid (CLA), a set of geometric isomers of a conjugated 18 carbon molecule, controls body composition in animals, in that it reduces body fat gain while increasing lean body mass gain. Park, Y., Regulation of energy metabolism and the catabolic effects of immune stimulation by conjugated linoleic acid, Ph.D. Thesis, University of Wisconsin-Madison(1996); Park, Y. et al., Lipids 32: 853–858(1997); Cook, M. E. et al., FASEB J. 12: A826(1998). The exact mechanism by which CLA affects body composition is unknown. Animals share a conserved mechanism for accumulating fat in fat cells (“adipocytes”), namely, the heparin-releasable lipoprotein lipase (LPL) enzyme located outside of the adipocytes breaks down triglycerides to fatty acids. The fatty acids are absorbed into the adipocytes and are converted into triacylglycerides (“fat”) for storage. CLA reduces body fat accumulation, in part, by inhibiting the LPL and stearoyl-CoA desaturase (SCD), thereby preventing adipocytes from storing fat. CLA also increases β-oxidation in skeletal muscle, and increases skeletal muscle mass. Park, Y. et al., Lipids 32: 853–858(1997). In addition to having these effects in mice, CLA also reduces fat accumulation in other animals such as human beings, pigs and dogs. Park, Y. et al., Lipids 34: 235–241(1999); Dugan, M. E. R. and J. L. Aalhus, Advances in Conjugated Linoleic Acid Research, Vol. 1: 354–368(1999); Ostrowska, E. et al., J. Nutr. 129: 2037–2042(1999); Schoenherr, W. and D. Jewell, FASEB J 13: A262(1999); Atkinson, R. L., Advances in Conjugated Linoleic Acid Research, Vol. 1: 348–353(1999); Blankson, H. et al., J. Nutrit. 130: 2943–2948(2000).
CLA also has many other biological activities including growth promotion activity, Chin, S. F. et al., J. Nutr. 124: 2344–2349(1994), anti-atherosclerosis activity, Lee, K. N. et al., Atherosclerosis 108: 19–25(1994); Nicolosi, R. J. et al., Artery 22: 266–277(1997), and anti-cancer activity, Ha, Y. L. et al., Cancer Res. 50: 1097–1101(1990); Ip, C. et al., Cancer Res. 51: 6118–6124(1991); Liew, C. et al., Carcinogenesis 16: 3037–3043(1995).
At a cellular level, CLA decreases the level of arachidonic acid (AA) in certain animal tissues. AA is oxidized by cyclooxygenase or by lipoxygenases to produce eicosanoid metabolites such as prostaglandin E2 (PGE2) and leukotrienes (LTs). The AA metabolism pathway and the activity of lipoxygenase in the pathway are conserved in animals. Eicosanoids have been implicated in the pathogenesis of a variety of human diseases, including cancer. Ara, G. and B. A. Teicher, Essential Fatty Acids 54: 3–16(1996); Fosslien, E., Annals Clin. Lab. Sci. 28: 67–81(1998); Steele et al., Cancer Epi. Biomarker Prev. 8: 467–483(1999); Myers, C. E. and J. Ghosh, Eur. Uro. 35: 395–398(1999). It has been suggested that CLA's anticancer mechanism may involve eicosanoid metabolism. Cook, M. E. et al., Poultry Sci. 72: 1301–1305(1993); Liu, K. -L. and M. A. Belury, Cancer Lett 127: 15–22(1998); Whigham, L. et al., FASEB J. 14: A728(2000).
Lipoxygenase inhibitor nordihydroguaiaretic acid (NDGA) was reported to reduce lipolysis, the fat degradation process, in fat tissue. Gowri, M. S. et al., Am. J. Physiol. Endocrinol. Metab. 279(3): E593-E600 (2000).